The technical field of this invention includes the treatment of disorders of the brain and spinal cord, e.g. diseases and disorders which may be remedied by treatment with secretory substances, such as neurotransmitters, conus peptides, neuromodulators, hormones, trophic factors, or growth factors or any compound, which can be produced by and secreted by a cell.
Encapsulated cell therapy is based on the concept of encapsulating cells, which secrete a biologically active factor for local delivery. The technology has the advantages of gene therapy through local and sustained delivery of the biologically active factor synthesised in situ by living cells, combined with retrievability, as the encapsulated cells can be removed again. A further advantage may comprise isolating cells from the recipient host's immune system by using an immunoisolatory capsule. An “immunoisolatory capsule” means that the capsule, upon implantation into a recipient host, minimises the deleterious effects of the host's immune system on the cells in the core of the device and minimises the deleterious effects of the cells in the core of the device on the host. Cells are immunoisolated from the host by enclosing them within implantable polymeric capsules formed by a microporous membrane. This approach prevents the cell-to-cell contact between host cells and implanted cells, reducing or eliminating antigen recognition through direct presentation.
Macroencapsulation involving loading of cells which secrete the active substance into capsules which are delivered through the cannula at the treatment site is an approach to long-term supply of biologically active substances locally e.g. In the brain or spinal cord. A major advantage of macroencapsulation is the retrievability of the capsule and U.S. Pat. No. 6,179,826 and others are concerned with different methods of surgically applying such capsules.
Typically, an insertion site is exposed surgically and a cannula, e.g. provided with an obturator is inserted to define a pathway from the insertion site to a treatment site. At this point the obturator is removed, and a capsule containing cells secreting a biologically active factor is positioned at the treatment site via the passageway. When the capsule is positioned, the cannula is removed. U.S. Pat. No. 6,179,826 discloses that a guidance needle may be inserted into the treatment site, and a guidewire is introduced into the lumen of the needle and is fed through until it enters the treatment site. Once the guidewire is contacting the treatment site, the guidance needle is removed and replaced with a cannula. After retraction of the guidewire, the cannula provides an insertion path for positioning a vehicle containing cells producing the active factors, at the desired site. The guidewire is removed and the vehicle is inserted into the cannula and guided along the pathway of the cannula towards the treatment site. The disclosed vehicle may include a capsule and an integral tether that extends from the capsule and which is of a length sufficient to reach at least from the treatment site to the proximity of the insertion site thereby facilitating fixation of the capsule at the insertion site, e.g. to the outer surface of the skull. The insertion site is subsequently covered by skin. In an alternative approach, the cannula is removed prior to the insertion of the capsule into the treatment site.
To facilitate that the capsule can be pushed into the treatment site by use of the tether, it may be necessary to stiffen the tether, e.g. by locating a small diameter wire portion of the pusher into a hollow cavity of the tether. Until now, the surgical operation, and e.g. the insertion of the wire into the tether is, however, critical and time-consuming, and the wire is only loosely inserted into the tether for subsequent removal when the capsule is in the right position at the treatments site. As the wire is loosely inserted there is also a risk that the wire may penetrate into the core of the device when pressure is applied to one end of the wire to insert the device.
Capsules with or without tethers of the kind known from the prior art have been stored and shipped in storage containers of the kind described in U.S. Pat. No. 5,681,740. The containers have securing means that secure the capsule and/or the tether to the bottom of the container. The securing means serve to avoid undue contact between the capsule and other system components. The securing means have a smaller diameter than the capsule/tether to secure the capsule in position in several places. A certain amount of manipulation is required to remove the capsule from the securing means, as it is fastened in several positions and at the bottom of the container. This may be done by using a forceps or similar surgical instrument. The use of surgical instruments in direct contact with implantable parts of the capsule for retrieval and later handling of the device represents a risk for damaging and contaminating the delicate parts prior to implantation at the treatment site.